Significant Population Differences Research Articles

Exploring cranial macromorphoscopic variation and classification accuracy in a South African sample

To date South African forensic anthropologists are only able to successfully apply a metric approach to estimate population affinity when constructing a biological profile from skeletal remains. While a non-metric, or macromorphoscopic approach exists, limited research has been conducted to explore its use in a South African population. This study aimed to explore 17 cranial macromorphoscopic traits to develop improved methodology for the estimation of population affinity among black, white and coloured South Africans and for the method to be compliant with standards of best practice. The trait frequency distributions revealed substantial group variation and overlap, and not a single trait can be considered characteristic of any one population group. Kruskal-Wallis and Dunn’s tests demonstrated significant population differences for 13 of the 17 traits. Random forest modelling was used to develop classification models to assess the reliability and accuracy of the traits in identifying population affinity. Overall, the model including all traits obtained a classification accuracy of 79% when assessing population affinity, which is comparable to current craniometric methods. The variable importance indicates that all the traits contributed some information to the model, with the inferior nasal margin, nasal bone contour, and nasal aperture shape ranked the most useful for classification. Thus, this study validates the use of macromorphoscopic traits in a South African sample, and the population-specific data from this study can potentially be incorporated into forensic casework and skeletal analyses in South Africa to improve population affinity estimates.

Analysis of network expression and immune infiltration of disulfidptosis-related genes in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a globally prevalent respiratory disease, and programmed cell death plays a pivotal role in the development of COPD. Disulfidptosis is a newly discovered type of cell death that may be associated with the progression of COPD. However, the expression and role of disulfidptosis-related genes (DRGs) in COPD remain unclear. The expression of DRGs was identified by analyzing RNA sequencing (RNA-seq) data in COPD. Further, COPD patients were classified into two subtypes by unsupervised cluster analysis to reveal their differences in gene expression and immune infiltration. Meanwhile, hub genes associated with disulfidptosis were screened by weighted gene co-expression network analysis. Subsequently, the hub genes were validated experimentally in cells and animals. In addition, we screened potential therapeutic drugs through the hub genes. We identified two distinct molecular clusters and observed significant differences in immune cell populations between them. In addition, we screened nine hub genes, and experimental validation showed that CDC71, DOHH, PDAP1, and SLC25A39 were significantly upregulated in cigarette smoke-induced COPD mouse lung tissues and bronchial epithelial cells (BEAS-2B) treated with cigarette smoke extract. Finally, we predicted 10 potential small molecule drugs such as Atovaquone, Taurocholic acid, Latamoxef, and Methotrexate. We highlighted the strong association between COPD and disulfidptosis, with DRGs demonstrating a discriminative capacity for COPD. Additionally, the expression of certain novel genes, including CDC71, DOHH, PDAP1, and SLC25A39, is linked to COPD and may aid in the diagnosis and assessment of this condition.

Historical fragmentation and stepping-stone gene flow led to population genetic differentiation in a coastal seabird.

Understanding the forces that shape population genetic structure is fundamental both for understanding evolutionary trajectories and for conservation. Many factors can influence the geographic distribution of genetic variation, and the extent to which local populations differ can be especially difficult to predict in highly mobile organisms. For example, many species of seabirds are essentially panmictic, but some show strong structure. Pigeon Guillemots (Cepphus columba; Charadriiformes: Alcidae) breed in small colonies scattered along the North Pacific coastline and feed in shallow nearshore waters year-round. Given their distribution, gene flow is potentially lower and population genetic structure is stronger than in most other high-latitude Northern Hemisphere seabirds. We screened variation in the mitochondrial control region, four microsatellite loci, and two nuclear introns in 202 Pigeon Guillemots representing three of five subspecies. Mitochondrial sequences and nuclear loci both showed significant population differences, although structure was weaker for the nuclear loci. Genetic differentiation was correlated with geographic distance between sampling locations for both the mitochondrial and nuclear loci. Mitochondrial gene trees and demographic modeling both provided strong evidence for two refugial populations during the Pleistocene glaciations: one in the Aleutian Islands and one farther east and south. We conclude that historical fragmentation combined with a stepping-stone model of gene flow led to the relatively strong population differentiation in Pigeon Guillemots compared to other high-latitude Northern Hemisphere seabird species. Our study adds to growing evidence that Pleistocene glaciation events affected population genetic structure not only in terrestrial species but also in coastal marine animals.

ScRNA-seq analysis discovered suppression of immunomodulatory dependent inflammatory response in PMBCs exposed to silver nanoparticles

The assessment of AgNPs toxicity in vitro and in vivo models are frequently conflicting and inaccurate. Nevertheless, single cell immunological responses in a heterogenous environment have received little attention. Therefore, in this study, we have performed in-depth analysis which clearly revealed cellular-metal ion association as well as specific immunological response. Our study didn’t show significant population differences in PMBC between control and AgNPs group implying no toxicological response. To confirm it further, deep profiling identified differences in subsets and differentially expressed genes (DEGs) of monocytes, B cells and T cells. Notably, monocyte subsets showed significant upregulation of metallothionein (MT) gene expression such as MT1G, MT1X, MT1E, MT1A, and MT1F. On the other hand, downregulation of pro-inflammatory genes such as IL1β and CCL3 in both CD16 + and CD16- monocyte subsets were observed. This result indicated that AgNPs association with monocyte subsets de-promoted inflammatory responsive genes suggesting no significant toxicity observed in AgNPs treated group. Other cell types such as B cells and T cells also showed negligible differences in their subsets suggesting no toxicity response. Further, AgNPs treated group showed upregulation of cell proliferation, ribosomal synthesis, downregulation of cytokine release, and T cell differentiation inhibition. Overall, our results conclude that treatment of AgNPs to PMBC cells didn’t display immunological related cytotoxicity response and thus motivate researchers to use them actively for biomedical applications.

Abstract B087: Targeting myeloid derived suppressor cell migration decreases tumor progression in a murine model of ovarian cancer

Abstract Introduction: High grade serous ovarian, fallopian tube and primary peritoneal carcinoma (HGSC) has an immunosuppressive and tumor promoting immune microenvironment. In this study, we have targeted the migration of myeloid derived suppressor cells (MDSC) through chemical inhibition of the CXCR2 chemotactic receptor to reverse the tumor-induced immunosuppression.Methods: ID8 cells with a p53 mutation (ID8-P53null) were used as a murine model of HGSC. ID8-p53null cells were injected intraperitoneally into immune intact C57/Bl6 mice, with 10 mice per group. After 7 days, mice were treated with cisplatin (cis, 1mg/kg, i.p., weekly), a CXCR2 inhibitor (CXCR2i, 4mg/kg, i.p., daily) or a combination of the 2 treatments. Necropsy was performed on day 29. The tumors were weighed, and the number of metastatic sites was quantified. The spleen and the tumor were resected, digested and flow cytometry was performed to evaluate the effects of treatment on the tumor immune microenvironment (TIME) as well as any systemic changes (evaluated by immune cells in the spleen). Granulocytic MDSC (G-MDSC) and monocytic MDSCs (M-MDSC) were defined as CD11b+Ly6G+,Ly6Clo and CD11b+Ly6G−Ly6Chi, respectively. One-way ANOVA with Tukey multiple comparisons was used for statistics with p<0.05 as the cut off for significance. Results: Tumor weights were significantly less in cis treated vs control mice (0.064g vs 0.220g, p <0.001) and CXCR2i treated vs control mice (0.171g vs 0.220g, p=.003). There was no additive effect of the CXCR2i to the cis treatment (cis 0.064g vs cis + CXCR2i 0.049g, p=0.62). The number of metastatic sites as a measurement of dissemination also decreased with cis or CXCR2i (number of sites: control: 47 vs cis: 12.7 vs CXCR2i: 32.5 vs cis + CXCR2i: 10.2). When the TIME was evaluated by flow cytometry, there were no significant differences in the immune populations including T-cells, NK cells, myeloid cells, and macrophages. However, there was a trend for cis to increase both the G-MDSC and M-MDSC populations and this effect was inhibited with the combination treatment of cis and CXCR2i. For the G-MDSC population control: 0.6% vs cis: 0.9% vs cis+CXCR2i: 0.5% and M-MDSC population control 3.4% vs cis: 6.8% vs cis+CXCR2i: 2.6%. Conclusion: CXCR2 is a chemotactic receptor present on MDSCs. We targeted this receptor to decrease the migration and infiltration of MDSCs into the ovarian cancer TIME. The CXCR2i decreased tumor progression in the ID8-p53null model of ovarian cancer. The TIME was evaluated by flow cytometry, and there was a trend for cis to increase the suppressive MDSC populations and this increase was inhibited by the CXCR2i. These exciting data suggest that traditional chemotherapy may lead to a more immunosuppressive TIME, which could have implications for future recurrence and treatment. Blocking the migration of immunosuppressive cells into the TIME may have a long-term impact on survival in HGSC. Survival studies in this murine model of HGSC are currently underway. Citation Format: Nicole Marjon, Railey Mikeska, Elizabeth R. Woodruff, Ritsuko Iwanaga, Tomomi Yamamoto, Benjamin G. Bitler. Targeting myeloid derived suppressor cell migration decreases tumor progression in a murine model of ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B087.

Zambia–Zimbabwe 2022 hippopotamus (Hippopotamus amphibius) and other species population distribution along Zambezi River

ABSTRACT A hippopotamus and other wildlife species survey were conducted in the Zambezi River between Kariba dam wall and Luangwa River confluence. The main objective of the survey was to establish hippopotamus and other wildlife species population distribution and densities along the Zambezi River. The boat survey method was used on both sides of the river in October 2022 for 262 km. Individual hippopotamus counted were 1769 on the Zambian side and 1424 on the Zimbabwean side. The Zimbabwean side recorded higher hippopotamus pods (138) than the Zambian side (123). Individual hippopotamus density was 26.60/km with a pod density of 0,45/km. There was a significant difference in hippo population between the five Zambezi River sections on the Zambian side ( x 2 = 2345, df = 4, p = 0.01) and Zimbabwean side ( x 2 = 538, df = 4, p = 0.01). The study established areas with high hippo and other wildlife species population distribution and densities, and the study helps to inform management of protected areas’ carrying capacities and management of Human Wildlife Conflicts. The study recommends more studies on hippopotamus migration, population demography, variation in home ranges and regular population surveys in both rivers and inland waterholes.

Impact of preexisting proteinuria on the development of regorafenib-induced problematic proteinuria in real-world metastatic colorectal cancer treatment

Regorafenib is the first multikinase inhibitor for treating metastatic colorectal cancer (mCRC). Proteinuria is a frequently encountered adverse effect, regardless of prior administration of vascular endothelial growth factor inhibitors. Herein, we aimed to assess the impact of baseline preexisting proteinuria on regorafenib-induced problematic proteinuria during real-world mCRC therapy. Patients with mCRC receiving regorafenib (n = 100) were retrospectively assessed and divided into control and preexisting proteinuria (baseline grade of 1–2) groups. The primary endpoint was the development of grade ≥ 2 (grade ≥ 3 in case of baseline grade 2 patients) proteinuria. Propensity score-matching was performed to confirm the robustness of primary analyses. Defined proteinuria occurred in 30.7 and 57.9% of patients in the control and preexisting proteinuria groups, respectively, with significant differences in the all-patient population (P = 0.01). The preexisting proteinuria group exhibited significant defined proteinuria development within 7 days of regorafenib initiation, grade ≥ 3 symptoms, and treatment suspension owing to proteinuria. Similar results were obtained in the propensity score-matched population. According to multivariate logistic regression analysis, baseline proteinuria was a singular risk factor for defined proteinuria development (adjusted odds ratio; 3.76, 95% confidence interval; 1.45–9.75, P = 0.007). Collectively, our study revealed that patients with preexisting proteinuria develop regorafenib-induced proteinuria degradation.

Loquat, a non-native plant in Türkiye, is a key seasonal host in the life cycle of Thrips hawaiiensis (Morgan, 1913) (Thysanoptera: Thripidae)

The Hawaiian flower thrips, Thrips hawaiiensis (Morgan, 1913) (Thysanoptera: Thripidae) is an important pest of several fruit crops in Türkiye’s Mediterranean region, one of the world’s major citrus-growing regions. In this study, the population fluctuation of T. hawaiiensis and other thrips species was investigated in citrus orchards, weeds, and nearby loquat trees. Results showed significant differences in populations of T. hawaiiensis among citrus varieties. The highest population density and damage ratio of T. hawaiiensis among citrus species were recorded in lemon variety (Kütdiken). Thrips hawaiiensis was detected on Daucus carota L. and Amaranthus albus L. among weeds as well as on flowers of loquat in the sampling area. The life cycle of T. hawaiiensis switched seasonally among citrus, weed, and loquat host plants. In addition, Melanthrips pallidior (Priesner, 1919) was the predominant species on weeds in the sampling area. These data suggest that T. hawaiiensis populations may be affected by climatic variations and hosts in and around the citrus orchard. The results are important in optimizing thrips monitoring and management strategies in citrus.

Effects of wilting on silage quality: a meta-analysis.

This meta-analysis aimed to evaluate the impact of wilted and unwilted silage on various parameters, such as nutrient content, fermentation quality, bacterial populations, and digestibility. Thirty-six studies from Scopus were included in the database and analyzed using a random effects model in OpenMEE software. The studies were grouped into two categories: wilting silage (experiment group) and non-wilting silage (control group). Publication bias was assessed using a fail-safe number. The results showed that wilting before ensiling significantly increased the levels of dry matter, water-soluble carbohydrates, neutral detergent fiber, and acid detergent fiber, compared to non-wilting silage (p<0.05). However, wilting significantly decreased dry matter losses, lactic acid, acetic acid, butyric acid, and ammonia levels (p<0.05). The pH, crude protein, and ash contents remained unaffected by the wilting process. Additionally, the meta-analysis revealed no significant differences in bacterial populations, including lactic acid bacteria, yeast, and aerobic bacteria, or in vitro dry matter digestibility between the two groups (p>0.05). Wilting before ensiling significantly improved silage quality by increasing dry matter and water-soluble carbohydrates, as well as reducing dry matter losses, butyric acid, and ammonia. Importantly, wilting did not have a significant impact on pH, crude protein, or in vitro dry matter digestibility.

Evaluation of Okra (Abelmoschus esculentus L.) Pest Control Strategies and Cost-Benefit Analysis

A field study on integrated pest management of okra insect pests was conducted at the Plant Pathology Research Institute, Ayub Agriculture Research Institute, in collaboration with the Department of Entomology, University of Agriculture Faisalabad, during the 2022 crop season. Rama Krishma, a variety of okra, was sown using the Randomized Complete Block Design with four replications and employing the drilling technique and agronomical practices. Significant differences (P0.05) in insect pest populations, namely whitefly, jassid, thrips, aphids, Helicoverpa, and spotted bollworm, were observed across various treatments. The pest populations of all these insects progressively decreased with treatment applications, and post-treatment measurements were taken 48 hours after each spray. The minimum mean populations of aphids (2.01/leaf), thrips (0.15/leaf), jassids (1.86/leaf), and spotted bollworm (2.41/plant) were recorded with the application of the biosal treatment, followed by Helicoverpa (1.25/plant) and whitefly (0.13/leaf) populations, which were observed in plots treated with tobacco extract and Chrysoperla + Trichogramma, respectively. The maximum mean populations of Formicomus antiqumus (0.55), Laius malleifer (0.17), Orius bugs (0.56), Trichogramma chilonis (Ishii) (20.41), Chrysoperla carnea (0.31), ladybird beetles (0.69), ants (0.79), and spiders (0.89) were recorded in the Chrysoperla + Trichogramma treated plots, indicating the safety of this bio-pesticide for predatory populations. Analysis of yield attributing parameters revealed that biosal-treated plots exhibited the highest values for several factors, including the maximum number of fruits per plant (19.57), number of flowers (8.75), squares (18.34), plant height (42.36 cm), and number of branches per plant (3.73). Furthermore, the cost-benefit ratios for okra plants were highest for treatments involving tobacco extract and natural enemies, with ratios of 1:16.3 and 1:10.6, respectively. The application of biosal after treatment demonstrated superior efficacy as a control approach compared to alternative treatments

A knowledge and preventive approach to COVID-19 and vaccination acceptance among Afghan immigrants in Iran

PurposeConsidering the importance of knowledge, attitudes and practice (KAP) in communities toward COVID-19 and the acceptance of COVID-19 vaccination in the control of this disease, this study aims to evaluate and compare the KAP level toward COVID-19 and the acceptance rate of COVID-19 vaccination between the Afghan immigrant population and IraniansDesign/methodology/approachThis cross-sectional descriptive study was conducted in 2021 on Afghan immigrants, Afghan-neighboring Iranians and Afghan nonneighboring Iranians. Of the 885 people who participated in the survey, 295 from each group were randomly selected. Data collection tools were the following questionnaires: KAP toward COVID-19 and acceptance and attitude toward COVID-19 vaccination.FindingsA total of 837 participants were included for data analysis. According to the findings, the KAP score on COVID-19 in Afghan immigrants was lower than the group of Iranians. Compared with Iranians, the score of nonneighboring Iranians was higher than the neighboring Iranians with Afghan immigrants. This difference in the mean scores suggests a statistically significant difference in the three groups (p < 0.0001). Among demographic data, the relationship between gender, education, type of job, income level and age with KAP indicated a significant difference in the total population studied. In the group of Afghan immigrants, the most likely reason for accepting the vaccination was the employer’s recommendation (55.63%). In comparison, the neighboring and nonneighboring Iranian groups with Afghan immigrants stated that they would receive the vaccine as soon as possible (49.22% and 63.22%, respectively).Originality/valueConsidering the low KAP score in the immigrant population in this study, these people are more vulnerable to the health and socioeconomic effects of COVID-19; therefore, the host countries have more challenges and responsibilities to protect these populations.

Abstract C078: Pembrolizumab response in melanoma patients: an analysis of the tumor microenvironment

Abstract Background: Melanoma has been associated with poor prognosis and limited treatment options. Immunotherapy, particularly the use of immune checkpoint inhibitors, has revolutionized the treatment landscape for advanced melanoma. Pembrolizumab, a PD-1 inhibitor, has shown promising results; however, the underlying mechanisms of its efficacy and the influence of the tumor microenvironment (TME) on treatment response remain incompletely understood. This study aims to investigate the response to pembrolizumab in melanoma patients and analyse the TME using a multiplexed immunofluorescence (mIF) spatial tissue analysis to gain insights into potential predictive factors and therapeutic targets. Methods: A retrospective analysis was conducted on formalin-fixed paraffin-embedded (FFPE) tumour samples from baseline melanoma patient samples, classified as responders (n = 6) or non-responders (n = 4) based on the response at 3 months post pembrolizumab treatment. Analysis was done using the mIF platform MultiOmyx™, a proprietary, immunofluorescence (IF) multiplexing assay that enables visualization and characterization of up to 60 biomarkers on a single FFPE section. Image segmentation, cell phenotyping, and spatial analytics were performed using our AI-powered image analytics software, NeoLYTX™. Results: Analysis of the 10 FFPE samples from metastatic melanoma patients treated with pembrolizumab revealed significant differences in immune cell populations between non-responders and responders. Patients who responded favorably to pembrolizumab exhibited increased infiltration of cytotoxic T lymphocytes (CTLs) and tumor-associated macrophages within the TME. This finding suggests that an immune-inflamed microenvironment, characterized by high levels of tumor-infiltrating lymphocytes may be indicative of a robust antitumor immune response. Moreover, immune checkpoint molecules PD-1, CTLA-4, LAG3, and TIM3 were also significantly increased in responding patients, suggesting potential therapeutic targets to enhance pembrolizumab response, including combination strategies targeting multiple immune checkpoints. When spatially characterizing T cell activation and exhaustion status in different regions of the TME we found an increase in checkpoint molecules among intra-tumoral CTLs as compared to intra-stromal CTLs. In particular, the fraction of CTLs with quadruple-positive CTLA4+LAG3+PD1+TIM3+ expression was doubled. This suggests an immunosuppressive TME in which CTLs are rapidly exhausted upon reaching the tumor. Work is now ongoing to characterize how this cell population spatially interacts with other immune and tumor cells in the TME. Conclusions: This study provides valuable insights into the response to pembrolizumab in melanoma patients and highlights the crucial role of the TME in determining treatment outcomes. Identification of immune cell subsets, and immunosuppressive mechanisms associated with pembrolizumab response may guide the development of novel therapeutic approaches to improve patient outcomes in advanced melanoma. Citation Format: Anna Juncker-Jensen, Juliana Wortman, Nigel Beaton, Kristina Beeler, Tobias Treiber, Mitchell Levesque, Julia Martinez Gomez, Jakob Vowinckel, Harry Nunns. Pembrolizumab response in melanoma patients: an analysis of the tumor microenvironment [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr C078.

The Non-Hematopoietic Content in Paediatric Autologous Hematopoietic Stem Cell Grafts Is Skewed Towards Regulatory Myeloid and Exhausted Phenotypes

Autologous hematopoietic stem cell transplant (aHSCT) is a central component of paediatric brain tumours and high-risk neuroblastoma management. Standardly, chemotherapy and G-CSF are used to mobilize the CD34+ hematopoietic stem/progenitor cells (HSC), which are used to support hematopoietic recovery following dose chemotherapy. Clinically, the graft infused is defined by solely by the CD34+ content. The non-hematopoietic passenger cells makeup most of the graft and are a mixture of myeloid and lymphoid cells that are potentially biologically active in the post-transplant setting. Here we study the content of the graft, focusing on the phenotypes of the cell populations, to begin to look at how the non-hematopoietic cells may facilitate anti-tumor activity, affect the tumour microenvironment, and/or immune recovery post-transplant. High parameter mass cytometry, with a custom 40-marker panel, was used to characterize 43 autologous cryopreserved grafts from children (median age 39 months, range 14-255 months) undergoing apheresis following chemotherapy and G-CSF mobilization. Healthy G-CSF-mobilized allogeneic donors (allograft) were used as a comparator group (n=10). Young children frequently have robust mobilization (peripheral blood CD34 count range from 100-1800 CD34/µL on day of collection) and generally one day collection will support multiple cycles of high dose therapy (target collections 20 x10 6 CD34+ cells/kg and often over collecting in 2-3 blood volume processed). This results in a product that is rich in CD34+ cells, with intergraft heterogeneity (median 7%; range 0.7-31%), compared to the CD34+ content of allografts (median 1.1%; range 0.3-2.4%) (autograft vs allograft median CD34 difference p&amp;lt;0.00005; Wilcoxon unpaired). There was variability in the non-hematopoietic component in the autografts (median T cells 10.8%; range 0.6 - 51.7%, and median monocytes 18.8%; range 4.1 - 51.4%). The allogeneic products were found to have less variability (T cells: 19.9 - 56%; monocytes: 7.3 - 19.6%). Autografts had increased expression of T cell exhaustion markers, with a median 30.8% (range 14.7 - 88.1%) of T cells expressing TIGIT and 35.1% (range 13.1 - 75.9%) expressing PD1 compared to the allografts (median TIGIT: 15.7%; range 9.3 - 28.7% and median PD1: 11%; range 4.2 - 19.7%). When grafts from high mobilizers (N= 21; &amp;gt;7% CD34+ cells) were analyzed by the actual number of cells infused they had had fewer regulatory cells: monocytic-myeloid derived-suppressor cells (M-MDSCs) (3.6x10 7 cells/kg; range 0.5 - 73.8x10 7; p&amp;lt; 0.0003), non-classical monocytes (0.9x10 7 cells/kg; range 0.5 - 21.3x10 7 cells/kg; p&amp;lt; 0.002) compared to the grafts from lower mobilizers (N = 22; &amp;lt;7.1% CD34+ cells) M-MDSC: median 7.7x10 7/kg; range 0.6 - 21.3x10 7 cells/kg, non-classical monocytes: 1.7x10 7 cells/kg; range 0.05 - 3.7x10 7 cells/kg). T cells and NK cells did not differ between high and low mobilizers. We are seeing significant differences in the regulatory cell populations infused in paediatric aHSCT based on the how robustly a patient mobilizes CD34+ cells after chemotherapy and G-CSF. It is not known whether these differences are clinically significant or affect anti-tumour immunity, tumour microenvironment perturbation, or immune recovery. With this high parameter mass cytometry strategy, we will be able to correlate engraftment kinetics and transplant outcomes (survival, relapse), which will allow us to re-envision how grafts should be optimally manufactured. Controllable variables include the timing of collection (earlier or later in the clinical course), alternative growth factor usage, enrichment or depletion of cell populations in the graft, or post-transplant growth factor administration. We suggest that the aHSCT graft can be thought of as an immunotherapy tool and not just for hematopoietic recovery.

Impact of Mangrove Deforestation on Fiddler Crab Distribution and Soil Physico-chemistry at Eagle Island, Rivers State

Mangrove forest in the Niger Delta and its associated biotic and abiotic has been greatly impacted by several factors, some natural and others anthropogenic in nature. Anthropogenic activities have negatively affected the organisms that inhabit the forest resulting in the decrease in size of population of fiddler crabs (Uca tangeri). To investigate the influence of anthropogenic activities on the mangrove habitat, burrow distribution and population of fiddler crabs and soil physico-chemistry were determined in forested and deforested sites. Burrows and number of crabs outside burrows were counted while samples of soil were retrieved and moved to the laboratory for the determination of cadmium (Cd), lead (Pb), total hydrocarbon content (THC) and Zinc (Zn) using atomic absorption spectrophotometer. The conclusions show a lack of significant difference in burrow distribution between forested and deforested areas (P&gt;0.05). Contrastingly there is significance in the difference in crab population in forested and deforested sites. (P&lt;0.05), which showed that there were more crabs in deforested areas than forested areas. There was also a significant difference in chemical and microbial population (P&lt;0.05). There was higher THC in deforested areas, which was probably impacted by the heavy-duty vehicles used to cut down the trees. The result implies that human activities of deforestation and pollution influence crab population and soil physicochemistry in mangrove forest.

Differential larval growth strategies and trophodynamics of larval Atlantic bluefin tuna (Thunnus thynnus) from two discrete spawning grounds

Atlantic bluefin tuna (ABT), Thunnus thynnus, is a globally important fishery resource. This oceanic top predator undertakes long-distance migrations from its nutrient-rich feeding grounds in the north Atlantic to oligotrophic spawning grounds. Larvae are born mainly in the corresponding ecosystems of its two well-established spawning areas: the Gulf of Mexico (GoM) and the Mediterranean Sea (MED). Stable isotopes analyses (SIA) of δ15N and δ13C have proven useful for understanding marine food webs and have evaluated larval ABT signatures in their respective spawning areas. This study is among the first to use larvae collected during the same spawning season (2014) from the GoM and one of the main spawning areas within the MED (the Balearic Sea) to standardize methodologies, compare larval growth, and relate SIA with larval postflexion growth using GAMs for the two spawning areas. The main findings identify significant population differences, with comparatively faster growth in GoM larvae. The GoM population had larger otoliths with wider increments, as well as higher δ15N values and higher trophic position for postflexion stages. Collectively, these findings highlight the importance of not only developing well-calibrated growth curves, but also integrating the distinct early life history dynamics for each spawning area to properly support ABT’s ongoing management efforts.

Mosquito surveillance on U.S military installations as part of a Japanese encephalitis virus detection program: 2016 to 2021.

Japanese encephalitis virus (JEV) continues to circulate throughout Southeast Asia and the Western Pacific where approximately 3 billion people in 24 countries are at risk of infection. Surveillance targeting the mosquito vectors of JEV was conducted at four military installations on Okinawa, Japan, between 2016 and 2021. Out of a total of 10,426 mosquitoes from 20 different species, zero were positive for JEV. The most abundant mosquito species collected were Aedes albopictus (36.4%) followed by Culex sitiens (24.3%) and Armigeres subalbatus (19%). Statistically significant differences in mosquito species populations according to location were observed. Changes in land use over time appear to be correlated with the species and number of mosquitoes trapped in each location. JEV appears to be absent from mosquito populations on Okinawa, but further research on domestic pigs and ardeid birds is warranted.

Characterization of gut microbiota profile in Iranian patients with bipolar disorder compared to healthy controls.

The human gut microbiota plays a crucial role in mental health through the gut-brain axis, impacting central nervous system functions, behavior, mood, and anxiety. Consequently, it is implicated in the development of neuropsychiatric disorders. This study aimed to assess and compare the gut microbiota profiles and populations of individuals with bipolar disorder and healthy individuals in Iran. Fecal samples were collected from 60 participants, including 30 bipolar patients (BPs) and 30 healthy controls (HCs), following rigorous entry criteria. Real-time quantitative PCR was utilized to evaluate the abundance of 10 bacterial genera/species and five bacterial phyla. Notably, Actinobacteria and Lactobacillus exhibited the greatest fold change in BPs compared to HCs at the phylum and genus level, respectively, among the bacteria with significant population differences. Ruminococcus emerged as the most abundant genus in both groups, while Proteobacteria and Bacteroidetes showed the highest abundance in BPs and HCs, respectively, at the phylum level. Importantly, our investigation revealed a lower Firmicutes/Bacteroidetes ratio, potentially serving as a health indicator, in HCs compared to BPs. This study marks the first examination of an Iranian population and provides compelling evidence of significant differences in gut microbiota composition between BPs and HCs, suggesting a potential link between brain functions and the gut microbial profile and population.

Abstract PO-088: TRPV1+ sensory neurons provide a tumor supportive environment through recruitment of MDSCs

Abstract Cancer neuroscience has become an increasing area of focus in cancer research as our understanding of the presence and function of intra-tumoral neurons continues to emerge, with studies indicating that tumor infiltrating neurons impact components of the tumor microenvironment promoting cancer initiation and progression. We have previously published that head and neck squamous cell carcinomas are innervated. We now focus on defining the contributions of intra-tumoral neurons to disease progression in HNSCC. Tumor implantation in a double transgenic mouse (TRPV1cre::DTAfl/wt) lacking the cancer-recruited TRPV1-expressing sensory neurons allows us to study the consequences of this neuronal loss on the local immune response. Importantly, comparison between wild type and TRPV1cre::DTAfl/wt mice demonstrated no significant immune population differences at baseline. Thus, wildtype and TRPV1cre::DTAfl/wt mice were orthotopically implanted with tumor and tumoral immune cell populations identified by flow cytometry. Cytokine and peptide concentrations were measured by ELISA. In vitro assays were preformed to molecularly define the neuronal signals and immune responses. Here, co-culture experiments of immortalized head and neck cancer cell lines and dorsal root ganglia (DRG) from wildtype mice were used to model tumor innervation in vitro. The media generated was applied to bone marrow derived (BMD) immune cells and the impact on immune cell phenotypes assayed by flow cytometry. Our orthotopic model demonstrates that the presence of HNSCC promotes a nerve-injury phenotype in ipsilateral trigeminal ganglion, demonstrated by increased expression of activating transcription factor 3 (ATF3). Utilizing a 12-color flow cytometry panel we show that tumors from TRPV1cre::DTAfl/wt mice harbor a significantly smaller population of myeloid derived suppressor cells (MDSCs) compared to those from wildtype animals. Further analysis demonstrates this population shift occurs primarily due to a decrease in the CD11b+ Ly6G+/Ly6Clo population. In vitro studies using BMD immune cells show that tumor cell-DRG co-culture conditioned media induces an expansion of the MDSC population compared to condition media from DRG or tumor cells alone. Additionally, transwell migration assays show that co-culture condition media also increases cellular migration compared to condition media from DRG or tumor cells alone. Moreover, ELISA analysis indicates that co-culture of tumor cells and DRG increases neuronal release of the neuropeptide, Substance P (SP), potentiating IL-6 release from tumor cells. In summary, we identified several mechanisms by which TRPV1-expressing intra-tumoral neurons promote MDSC infiltration at the tumor bed and promote disease progression. These mechanisms define targets for therapeutic intervention including SP and IL-6 signaling. Future studies will test the clinical utility of these targets. Together, our data suggests that intra-tumoral neurons contribute to cancer progression through generation of a tumor supportive microenvironment. Citation Format: Anthony C. Restaino, Maryam Ahmadi, Sebastien Talbot, Paola D. Vermeer. TRPV1+ sensory neurons provide a tumor supportive environment through recruitment of MDSCs [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-088.

Budget Impact Analysis of Risperidone Use and Adverse Event Monitoring in Autism Spectrum Disorder in Brazil: Assessment of Theoretical Versus Real Data.

Risperidone is used in autism spectrum disorder (ASD) to manage aggressive behavior. Budget impact analysis (BIA) assists managers in promoting more sustainable health systems; however, it is unclear whether BIAs underestimate or overestimate the estimates derived from real-world data. This study aimed to compare the estimated BIA values of risperidone use and the monitoring of adverse events in ASD using theoretical and real data. Analyses were conducted based on the clinical protocol and the Brazilian therapeutic guidelines for ASD. The perspective adopted was that of the Unified Health System (SUS), considering a time horizon of 5 years. Three possible scenarios were considered based on the maximum daily dose of risperidone. Expenses related to the acquisition of risperidone and the monitoring of adverse events were taken into account using health databases in Brazil. For the calculation based on theoretical data, the prevalence of ASD was estimated using information from the scientific literature and the Brazilian demographic census. The model calculated from real data was obtained by analyzing the linear trend of the number of users assisted in the SUS from 2017 to 2021. The population estimated by the theoretical model compared with the model calculated from the real data was higher. Likewise, the 5-year budgetary impact of the theoretical model versus the model calculated from the real data was higher, with statistical significance in all scenarios (p<0.001). In the real data model, the most economically advantageous scenarios were Scenario 1 for children (International dollars [I$]7,630,040.73) and Scenario 3 for adults (I$60,329,288.17). Estimated expenditures for monitoring adverse events ranged from 17 to 74% in children and from 50% to 63% in adults. The data revealed significant differences in population and cost estimation between theoretical data and real-world data. The expenses associated with monitoring adverse events represented a substantial expenditure estimate for the SUS.

Molecular Profile of Variants in CDH1, TP53, PSCA, PRKAA1, and TTN Genes Related to Gastric Cancer Susceptibility in Amazonian Indigenous Populations.

Gastric Cancer is a disease associated with environmental and genetic changes, becoming one of the most prevalent cancers around the world and with a high incidence in Brazil. However, despite being a highly studied neoplastic type, few efforts are aimed at populations with a unique background and genetic profile, such as the indigenous peoples of the Brazilian Amazon. Our study characterized the molecular profile of five genes associated with the risk of developing gastric cancer by sequencing the complete exome of 64 indigenous individuals belonging to 12 different indigenous populations in the Amazon. The analysis of the five genes found a total of 207 variants, of which 15 are new in our indigenous population, and among these are two with predicted high impact, present in the TTN and CDH1 genes. In addition, at least 20 variants showed a significant difference in the indigenous population in comparison with other world populations, and three are already associatively related to some type of cancer. Our study reaffirms the unique genetic profile of the indigenous population of the Brazilian Amazon and allows us to contribute to the conception of early diagnosis of complex diseases such as cancer, improving the quality of life of individuals potentially suffering from the disease.